Compositions and Methods for Treatment of Prediabetes

ABSTRACT

The invention provides compositions and methods to treat prediabetes. In particular, the invention has discovered that particular combinations of diverse types of antioxidants have synergistic and surprising effects for use against prediabetes. The diverse types of antioxidants include: antioxidants that comprise stabilizing heteroatoms; antioxidants with conjugated segments of alternating single and double bonds; antioxidants with disulfides; and antioxidants with phenolic groups. In particularly useful embodiments one or more of the antioxidants that comprise stabilizing heteroatoms have pro-oxidant effects, e.g., in the liver.

RELATED APPLICATIONS

This application claims priority to provisional U.S. patent application No. 62/327,421, filed Apr. 25, 2016, having the same title and inventor.

FIELD OF THE INVENTION

The invention concerns compositions and methods for the treatment and prevention of prediabetes.

BACKGROUND

Prediabetes is a condition characterized by abnormally high yet less than extreme blood sugar levels, (i.e., in the range of 100 to 125 mg/dL). Prediabetic patients lack one or more symptoms that characterize diabetes, however but the condition is often a prelude to type 2 diabetes mellitus (T2DM). A quarter of the cases commonly progress to T2DM within 3 to 5 years, and half within 10 years. Prediabetes may be identical to metabolic syndrome, however the latter is evaluated by a different set of biomarkers.

A common symptom of prediabetes is impaired fasting glucose (IFG), in which blood sugar levels are high but still below those typical of diabetes. Many IFG patients retain normal responses to a glucose tolerance test. Another common system is impaired glucose tolerance (IGT) associated with insulin resistance and elevated cardiovascular risk. Among American adults over 40 years of age, 33% have IFG, 15% have IGT, and 40% are prediabetic (i.e., they have IFG and/or IGT).

Despite those diagnostic conditions the symptoms of prediabetes are often not distinctive. Thus a range of signs are monitored: persistent hunger; obesity; weight gain or at the other extreme, unexplained weight loss; flu-like weakness and fatigue; blurry vision; slowness of healing for cuts and bruises; tingling or insensate extremities; and recurring infections of the skin, gums, bladder or vagina.

Prediabetes is associated with many possible causes beyond high blood sugar, and these range from sleep disorders, genetics, cardiovascular disease, hypertension, high triglyceride levels, low HDL cholesterol, elevated weight, pregnancy, high birth weight, polycystic ovarian syndrome.

The lifestyle intervention guidelines to prevent the onset of type 2 diabetes include: dietary regimes that are low in sugar, refined carbohydrates, saturated fats, salt and total calories; regular physical exercise, for instance 30 minutes per day five days per week; and weight reduction even by as little as a few percent.

The prevalence of prediabetes remains high despite widespread medical monitoring and health education, and methods to treat it have been lacking apart from the lifestyle changes just discussed. Consequently there is an ongoing need for compositions to treat and prevent 5 prediabetes.

SUMMARY OF THE INVENTION

The invention provides compositions and methods to treat and prevent development of prediabetes. In particular, the present invention has discovered that particular combinations of 10 diverse types of antioxidants that have synergistic and surprising effects for use against prediabetes. The diverse types of antioxidants include: antioxidants that comprise stabilizing heteroatoms; antioxidants with conjugated segments, i.e., segments in which double bonds alternate with single bonds; antioxidants with disulfide bonds; and antioxidants with phenolic groups. It has further been discovered that it is beneficial to use antioxidants that facilitate an oxidative balance, i.e., that have pro-oxidant effects, e.g., in the liver.

Particularly suitable compositions for the invention include a combination of each of the ingredients indicated in Table I.

TABLE I Taurine in a range of 40-360 mg; a non- limiting illustrative quantity is 200 mg. Taurine is an antioxidant that comprises a stabilizing heteroatom, relieves oxidative stress, and has a pro-oxidative effect in the liver.

Beta-alanine in a range of 10-90 mg; a non- limiting illustrative quantity is 50 mg. Beta- alanine is an anti oxidant that comprises a stabilizing heteroatom.

Acetyl-L-carnitine in a range of 20-180 mg; a non-limiting illustrative quantity is 100 mg. Acetyl-L-carnitine is an antioxidant that comprises a stabilizing heteroatom, relieves oxidative stress, and has a pro-oxidative effect in the liver.

Agmatine in a range of 25-225 mg; a non- limiting illustrative quantity is 125 mg. Agmatine is an antioxidant that comprises a stabilizing heteroatom.

Grape seed extract in a range of 10-90 mg; a non-limiting illustrative quantity is 50 mg. Grape seed extract comprises phenolic antioxidants, such as for instance, (−)- epicatechin and oligomers of (−)-epicatechin.

L-camosine in a range of 5-45 mg; a non- limiting illustrative quantity is 25 mg. L- camosine is an antioxidant that comprises a stabilizing heteroatom, and is active against reactive organic species (ROS) radicals.

Vitamin D3 in a range of 500-4500 I.U.; a non-limiting illustrative quantity is 2500 I.U. Vitamin D3 is an antioxidant with conjugated hydrocarbon segments.

Methylcobalamin (a form of Vitamin B12), 20-220 μg; a non-limiting illustrative quantity is 120 μg. Methylcobalamin is an antioxidant that comprises a conjugated segment; the segment contains nitrogen atoms and among other properties can bind the oxidant nitric oxide (NO).

Methylcobalamin

In particular embodiments compositions of the invention include a combination of each of the ingredients indicated in both Tables I and II.

TABLE II

Alpha-Lipoic Acid in a range of 50-450 μg; a non-limiting illustrative quantity is 500 μg. Alpha-Lipoic Acid is a disulfide-type antioxidant

The embodiments of the invention as described herein are merely illustrative and are not exclusive. Numerous additions, variations, derivations, permutations, equivalents, combinations and modifications of the above-described invention will be apparent to persons of ordinary skill in the relevant arts and are within the scope and spirit of the invention. The invention as described herein contemplates the use of those alternative embodiments without limitation. 

1) An improved composition for treatment of prediabetes comprising at least four types of antioxidant compounds, characterized in that: a) at least one of the antioxidant compounds comprises a stabilizing heteroatom adjacent to a saturated carbon, wherein if the heteroatom is sulfur it is not part of a disulfide bond; b) at least one of the antioxidant compounds comprises a conjugated segment; c) at least one of the antioxidant compounds comprises a disulfide bond; and d) at least one of the antioxidant compounds comprises a phenolic group; wherein: i) at least one of the antioxidant compounds has a pro-oxidant effect in the liver; and ii) a pharmaceutically effective amount of the composition is effective to reduce or mitigate at least one symptom of prediabetes. 2) The composition of claim 1 wherein the stabilizing heteroatom is selected from the group consisting of nitrogen, sulfur and oxygen. 3) The composition of claim 1 wherein the at least one antioxidant compound comprising a stabilizing heteroatom adjacent to a saturated hydrocarbon is selected from the group consisting of taurine, beta-alanine, acetyl-L-carnitine, agmatine and L-carnosine. 4) The composition of claim 1 wherein the at least one antioxidant compound comprising a conjugated segment is selected from the group consisting of vitamin D compounds, cobalamin compounds and carotenoids. 5) The composition of claim 1 wherein the at least one antioxidant compound comprising a conjugated segment is selected from the group consisting of vitamin D3, methylcobalamin, and lutein. 6) The composition of claim 1 wherein the at least one antioxidant compound comprising a disulfide bond is alpha-lipoic acid. 7) The composition of claim 1 wherein the at least one antioxidant compound comprising a phenolic group is selected from the group consisting of epicatechin, oligomers of epicatechin, and other epicatechin derivatives found in grape seed extract. 8) The composition of claim 1 wherein the at least one antioxidant compound comprising a phenolic group is provided in the form of grape seed extract. 9) The composition of claim 1 wherein the composition comprises: a) taurine in an amount selected from the range of 40 to 360 mg; b) beta-alanine in an amount selected from the range of 10 to 90 mg; c) acetyl-L-carnosine in an amount selected from the range of 20 to 180 mg; d) agmatine in an amount selected from the range of 25 to 225 mg; e) grape seed extract in an amount selected from the range of 10 to 90 mg; f) L-carnosine in an amount selected from the range of 5 to 45 mg; g) vitamin D3 in an amount selected from the range of 500 to 4,500 I.U.; and h) methylcobalamin in an amount selected from the range of 20 to 220 μg. 10) The composition of claim 9 wherein the composition further comprises: a) lutein in an amount selected from the range of 1 to 9 mg; and b) alphalipoic acid in an amount selected from the range of 100 to 900 μg. 11) The composition of claim 1 wherein the composition comprises: a) taurine in an amount of 200 mg; b) beta-alanine in an amount of 50 mg; c) acetyl-L-carnosine in an amount of 100 mg; d) agmatine in an amount selected of 125 mg; e) grape seed extract in an amount of 50 mg; f) L-carnosine in an amount of 25 mg; g) vitamin D3 in an amount of 2,500 I.U.; h) methylcobalamin in an amount of 120 μg; i) lutein in an amount of 5 mg; and j) alphalipoic acid in an amount of 500 μg. 12) A method for treatment of prediabetes comprising administration of a composition comprising at least four types of antioxidant compounds, characterized in that: a) at least one of the antioxidant compounds comprises a stabilizing heteroatom adjacent to a saturated carbon, wherein if the heteroatom is sulfur it is not part of a disulfide bond; b) at least one of the antioxidant compounds comprises a conjugated segment; c) at least one of the antioxidant compounds comprises a disulfide bond; and d) at least one of the antioxidant compounds comprises a phenolic group; wherein: i) at least one of the antioxidant compounds has a pro-oxidant effect in the liver; and ii) a pharmaceutically effective amount of the composition is effective to reduce or mitigate at least one symptom of prediabetes. 13) The composition of claim 12 wherein the stabilizing heteroatom is selected from the group consisting of nitrogen, sulfur and oxygen. 14) The composition of claim 12 wherein the at least one antioxidant compound comprising a stabilizing heteroatom adjacent to a saturated hydrocarbon is selected from the group consisting of taurine, beta-alanine, acetyl-L-carnitine, agmatine and L-carnosine. 15) The composition of claim 12 wherein the at least one antioxidant compound comprising a conjugated segment is selected from the group consisting of vitamin D compounds, cobalamin compounds and carotenoids. 16) The composition of claim 1 wherein the at least one antioxidant compound comprising a conjugated segment is selected from the group consisting of vitamin D3, methylcobalamin, and lutein. 17) The composition of claim 1 wherein the at least one antioxidant compound comprising a disulfide bond is alpha-lipoic acid. 18) The composition of claim 1 wherein the at least one antioxidant compound comprising a phenolic group is selected from the group consisting of epicatechin, oligomers of epicatechin, and other epicatechin derivatives found in grape seed extract. 19) The composition of claim 1 wherein the at least one antioxidant compound comprising a phenolic group is provided in the form of grape seed extract. 20) The composition of claim 1 wherein the composition comprises: a) taurine in an amount selected from the range of 40 to 360 mg; b) beta-alanine in an amount selected from the range of 10 to 90 mg; c) acetyl-L-carnosine in an amount selected from the range of 20 to 180 mg; d) agmatine in an amount selected from the range of 25 to 225 mg; e) grape seed extract in an amount selected from the range of 10 to 90 mg; f) L-carnosine in an amount selected from the range of 5 to 45 mg; g) vitamin D3 in an amount selected from the range of 500 to 4,500 I.U.; and h) methylcobalamin in an amount selected from the range of 20 to 220 μg. 21) The composition of claim 9 wherein the composition further comprises: a) lutein in an amount selected from the range of 1 to 9 mg; and b) alphalipoic acid in an amount selected from the range of 100 to 900 μg. 22) The composition of claim 1 wherein the composition comprises: a) taurine in an amount of 200 mg; b) beta-alanine in an amount of 50 mg; c) acetyl-L-carnosine in an amount of 100 mg; d) agmatine in an amount selected of 125 mg; e) grape seed extract in an amount of 50 mg; f) L-carnosine in an amount of 25 mg; g) vitamin D3 in an amount of 2,500 I.U.; h) methylcobalamin in an amount of 120 μg; i) lutein in an amount of 5 mg; and j) alphalipoic acid in an amount of 500 μg. 